Acylation of aminosulfonic acids



Patented Oct. 30., 1951 ACYLATION OF AMINOSULFONI C ACIDS OFDIBENZOTHIOPHENE Mario Scalera and Warren S. Forster,Somerville,

N. .L, assignors to American Cyanamid Company, New York, N. Y., acorporation of Maine No Drawing. Application April 4, 1950,

Serial'No. 153,988

- 9 Claims. 1

This invention relates to the acylation of aminosulfonic acids. Moreparticularly, it is concerned with the diacylation of diaminosulfonicacids of the dibenzothiophenedioxide series.

Many of the compounds of theftypes of the present invention areimportant dyestuff intermediates. Many of their a'cylated derivativespossess marked fluorescent properties, and are useful in overcoming theyellowish cast which often develops in white materials, especiallycellulosic fabrics. These compounds are not claimed per se as part ofthe present invention, but do form in part the subject matter of thecopending applications for United States Letters Patent of Scalera andEberhart, Serial No. 45,425, filed August 20, 1943, now U. S. Patent No.2,563,795, and Serial No. 168,392.'filed June 15, 1950, now U. S. PatentNo. 2,563,493.

Despite their desirability, commercial exploitation of these materialshas been hampered by the lack of a good method for theirpreparation.Although many aminosulfonic acids are readily acylated with acid halidesin aqueous solution, 3,7 diaminodibenzothiophenediozids-2,8disulfonicacids cannot be satisfactorily acylated in this way. Further, the use oforganic solvents proved not to be very satisfactory in this reaction,apparently because of the great insolubility of the starting material,and the inertness of the amino groups to'acylation under theseconditions. Consequently the need has persisted for a simple andpractical way of preparing these diacyl derivatives.

In general, the object of the present invention has been accomplished bycarrying out the acylation in a non-polar solvent, on certain organicbase salts of 3,7-diaminodibenzothiophenedioxide-2,8-'disulfonic acids.In view of the difficulties encountered in the past, the effectivenessof the modified process of the present invention is particularlysurprising. Products of excellent quality are obtained in surprisinglyhigh yield.

The exact cause for this surprising result is not entirely clear. Whilethe use of the organic base appears to have the effect of breaking upthe stable Zwitter ion structure of the diaminosulfonic acid, thiscannot be the entire explanation. The Zwitter ion is also destroyed whenthe diaminosulfonic acid is dissolved in aqueous alkali, and yet suchalkaline solutions cannotbe acylated, any attempt to force the reactionresulting only in the decomposition of the acid halide. It may be thatsteric hindrance plays a part in this great dificulty of acylation; andthat this steric hindrance can only be overcome by acylation at elevatedtemperatures, which is made possible by the present method of operationin which there is no danger of hydrolyzing the acid chloride.

In any event, by converting the diaminosulfonic acid to its salt withthe organic base, and treating the resulting salt with the acyl halidein a non-polar solvent, the desired acylation is accomplishedsuccessfully. The reaction gives excellent yields using a minimum excessof acid halide. The product is obtained substantially free fromundesirable impurities. While the salt with the organic base may andperhaps preferably will be preformed, if desired it may also be formedin situ in the solvent. In the latter case, it is not certain just howfar towards comple-- tion salt formation actually proceeds, but thepractical results in producing the desired product are equallysatisfactory.

According to the present invention, tertiary amines are particularlyeffective. This may be partly because they do not react with the acidhalides to form stable acylated products, although they may formaddition compounds. Such amines can be used to form well-defined saltswith the 3,7-diaminodibenzothiophenedioxide- 2,8-disulfonic acid. Thesesalts are smoothly acylated with aroyl halides in organic solvents.

the present invention if it is volatile with steam.

As a practical limitation, it is generally, but not always, found thatif the boiling point of the amine is much above 200 C. its steamvolatility is too low to give the best results in this invention. Amongthe suitable amines for the purpose of the present invention may beincluded triethylamine, pyridine, benzyldimethylamine, dimethylaniline,tripropylamine, N-ethylmorpholine, N- ethylpiperidine,cyclohexydimethylamine, diet-hylaniline, thiazole, the picolines, andthe like.

A number of solvents are suitable for the acylation process of thepresent invention. It is essential that they be stable to the reactants.In general, organic solvents boiling above about C. are to be preferred.Suitable solvents include both aliphatic and aromatic hydrocarbons andtheir halogeno and nitro derivatives, as well as esters, ethers, andketones. By way of illustrative examples, the following solvents areeffective: benzene, monoand dichlorobenzene and the dichlorotoluenes;the xylenes; nitrobenzene and the nitrotoluenes; cymene, benzonitrile,ethyl benzoate, acetophenone, cyclohexanone, and anisole. A wide varietyof diaminodibenzothiophenedioxide sulfonic acids may be successfullyacylated in accordance with the process of the present invention.Typical examples of these acids include the following:3,7-diaminodibenzothiophenedioxide-2-sulfonic acid, 3,7-diaminodibenzothiophenedioxide-2,8-disulfonic acid and chloroderivatives.

As has been mentioned, the process of the present invention isespecially useful with acid halides, particularly chlorides ofalkoxy-substituted benzoic acids. There may be one or morealkoxysubstituents, usually, but not necessarily, containing about oneto four carbon atoms. Typical examples of such halides include: ;theisomeric anisoyl chlorides, o-ethoxybenzoyl chloride, o-propyloxybenzoylchloride, and 2,4- and 2,5-dimethoxy benzoyl chlorides. Y

It is an advantage of the present invention that the salts can beprepared by any suitable method. For example, the3,7-diaminodibenzothiophenedioxide-2,8-disulfonic acid can be dissolvedin water as its alkali salt and treated in aqueous solution with thesalt forming base. In many casesthe desired salt'crystallizes directlyfrom the solution. In other cases evaporation may be necessary. It isnot necessary forthe purpose of this invention that the salt be strictlypure. l 1

The organic salt is readily dispersed in the selected organic solvent.An addition of, some excess free amine is often found advantageous,however it may be a different amine from the one used for saltformation. Another desirable practice at this point is to remove anywater present by distilling apart of the solvent.

As was noted above, the salt can alsobe prepared by mixing thedisulfonic'acid and the organic base, either in stoichiometric amount orin excess, directly in the organic solvent. A short heating period atthis stage is found usually desirable, though not always necessary. Thesalt will form, at least to the extent required to initiate and maintainacylation. i

In either case, acylation isthen readily effected by admixing theselected aroyl halide'and the salt, or the salt-forming mixture in thepresence of the solvent. heating should be maintained until reactionsubstantially ceases. Reaction is very slow below about 60. C.Temperaturesjust short of those producing volatilization. of solventand/or reactants are to be preferred. The reaction mixture can then beworked up by the usual'known cussed in conjunction with the followingspe-, These are intended as illustra tive and not by way of limitation.Except as,

ciflc examples.

otherwise noted, all parts arehy weight.

Stirring and preferably, also,

and their alkyl Example 1 ON- 1Y0 or'r H r 0 02135 2 CzH Q 3,7diaminodibenzothiophenedioxide 2,8-disulfonic acid is dissolved indilute sulfuric acid and treated with triethylamine. The triethylaminesalt crystallizes from the cold solution, and is filtered and dried. Aslurry of 30.4 parts of the resulting salt in 134 parts of chlorobenzeneand 30.3 parts of triethylamine is heated under reflux with stirring andto it is added during about 30 minutes 27.? parts of ortho-ethoxybenzoylchloride. The reaction mixture is heated under reflux for four hours andthen to it is added an additional portion of 30.3 parts of triethylamineand 27.7 parts of ortho-ethoxybenzoyl chloride. Refluxing andstirringare continued overnight. The chlorobenzene and tri-' ethylamine are thenremoved by steam distilla: tion after adding sufflcient sodium carbonateto render the mixture alkaline to brilliant yellow.

The product is isolated in excellent yield in the usual mannerbyfiltration, washing with 2% brine and drying.

Example 2 A slurry of 122 parts of3,7-diaminodibenzothiophenedioxide-2,8-disulfonic' acid, 157 parts ofpyridine, and 1110 partsof monochlorobenzene is heated at reflux minutesbefore adding a solution of 185 parts of'2A-dimethoxybenzoyl chloride in220 partsof chlorbenzene.

resents an excellent yield of 3,7-di(2,4-dimethoxybenzoylamine)dibenzothiophenedioxide+2,8-

disulfonic acid.

Example 3 The trimethylamine salt of 3,7-dia'minodi5'benzothiophenedioxide 2,8 disulfonic acid is prepared by treatment withexcess of aque ous trimethylamine solution and evaporation to dryness.The salt is acylated by heating with 2,4-diethoxybenzoyl chloride inchlorobenzene,

as described in Example 2. The mixture is then treated with soda ash andsteam distilled to re- 3,7-diaminodibenzothiophenedioxide 2,8 disulfonicacid is dissolved in dilute sulfuric acid and treated withtriethylamine. The triethylamine salt crystallizes from the coldsolutionL 15.2 parts of the salt is slurried in 10 parts of pyridine andparts.-

and is filtered and dried.

of. chlorobenzene. After heating to reflux/the mixture is graduallytreated with'20.2 parts of oephenylbenzoyl chloride. Heating andstirring are continued until acylation is complete. The resulting slurryis made alkaline with aqueous sodium carbonate and steam distilled toremove the solvents. The product is then salted out with sodiumchloride, filtered, washed with brine, and dried.

Example 5 nso; solrr OON- Noo H g H 0000113 oo00m,

A mixture of 10.4 parts of pyridine, 83 parts of chlorobenzene and 10.1parts of the tri'ethylamine salt of3,7-diaminodibenzothiophenedioxide-2,8- disulfonic acid is heated toreflux and treated with 15.9 parts of o-carbomethoxybenzoyl chloride.product is separated, dissolved in aqueous sodium carbonate and saltedout with sodium chloride. It is then filtered and dried.

I Example 6 HSOz sonar re s d H 02 H CHaO- 001% 43GB}; 50H:

'A slurry 0f 16 parts of pyridine, 110 parts'of chlorobenzene, and 15.2parts of the triethylamine salt of3,7-diaminodibenzothiophenedioxide-2,8-'disulfonic acid is heated toreflux and gradually treated with a solution of 18.5 parts of2,4-dimethoxybenzoyl chloride in 22 parts of chlorobenzene.

When acylation is completed, the solid When acylation is complete,--as

gradually treated with 15.4 parts or phenoxyacetyl chloride. Whenacylation is complete the mixture is cooled, made alkaline with sodiumcarbonate, and subjected to steam distillation. The product is saltedout in the usual way and filtered.

. Example 8 HS 0. SOaH NO-OC ON- NOC- CN I H H A mixture of 16 parts ofpyridine, 145 parts of chlorobenzene, and 15.2 parts of thetriethylamine salt of3,7-diaminodibenzothiophenedioxide-2,8-disulfonicacid is heated toreflux and gradually treated with 16.7 parts of pcyano benzoyl chloride.After three hours of stirring and refluxing, the mixture is cooled, madealkaline with sodium carbonate solution, and subjected to steamdistillation. The brightyellow product is then salted out with sodiumchloride, filtered, washed with brine, and dried. It is obtained inexcellent yield.

Example 9 H803 sari Example 10 HS 02 803E CsHsS 02- C ON- NO COS 02C 0H!l H 02 "H shown by the disappearance of any test for primary aminogroups, the mixture is cooled, made alkaline with aqueous sodiumcarbonate, and subjected to steam distillation. Theproduct is thensalted out by the addition of sodium chloride.

Example 7 otrrsoomo 01 S/ *i ooomoofim H 02 H A mixture of 145 parts ofchlorobenzene, 16 parts of pyridine, and 15.2 parts of the triethylaminesalt of 3,7-diaminodibenzothiophenediox- A slurry of 7.6 parts of thetriethylamirie salt of 3,7vdiaminodibenzothiophenedioxidea2,8-disulfonic acid, inlO parts ofpyridine, and .225 parts of chlorobenzene, is heated to 80 C. andtreated slowly with 12.7 parts of p-phenylsulfonylbenzo'yl chloride.Acylation is completed at reflux temperature, the .mixture then beingtreated with aqueous sodium carbonate, and steam distilled free ofpyridine. The yellow product is salted out by the addition of sodiumchloride, filtered, washed, and .dried.

Example 11 10.1 parts of the triethylamine salt of 3,7-diaminodibenzothiophenedioxide 2,8 disulfonic acid is slurried in 2'75parts of chlorobenzene and ide-2,8-disulfonic acid is heated to refluxand 15 parts of pyridine and heated to reflux. To this is graduallyadded 10.9 parts of p-methylsulfonylbenzoyl chloride. When acylation iscomplete,'the mixture is treated with aqueous sodium'carbonate and steamdistilled free of pyridine; The yellow product is salted out with sodiumchloride and filtered and dried.

Example 12 HSO SOzH COIYT IITOC- SOzCH3 S O: H

Example 13 ceding examples. After completion of acylation, the mixtureis treated with 10% sodium carbonate solution and freed of pyridine bysteam distillation. The product is isolated in the ordinary manner.

We claim:

1. The method of acylating a sulfonic acid of3,7-diaminodibenzothiophenedioxide which comprises admixing an aroylhalide and a member from the group of (a) mixtures of the selectedaminosulfonic acid with a steam-volatile tertiary amine, and (b) saltsof a steam-volatile tertiary amine and the selected aminosulfonic acid,in the presence of an inert organic solvent under substantiallyanhydrous conditions; maintaining the mixture under reaction conditionsuntil reaction substantially ceases and isolating the reaction product.

. 7 HS 03 sm-n cH=C -soiN NS 02-6-0213 I s I A mixture of 15.2 parts ofthe triethylamine salt, prepared as described above, 150 parts ofchlorobenzene, and 16 parts of pyridine is stirred and refluxed whilebeing treated with 22 parts of p-toluenesulfonyl chloride. The reactingmixture is worked up in the usual manner, giving a pale green product.

Example 14 13.2 parts of thiophene-2-carboxylic acid chloride. Afterstirring and refluxing for three hours the mixture isworked up in theusual manner.

Q A mixture of 150 parts of chlorobenzene, 16 parts of pyridine, and15.2 parts of the triethylamine salt prepared as described in the aboveexamples, is stirred and refluxed while being treated with 17.2 parts ofZ-naphthoyl chloride. The reaction is completed and the product workedup asrdescribed in the above examples.

Example 16' A mixture of' 10 parts of chlorobenzene, 22 parts ofdiaminodimethyldibenzothiophenedioxide disulfonic acid, and 100 parts ofpyridine is treated with 26 parts of para anisoyl chloride and refluxed,according to the procedure of the pre- 2. The method of aroylating asulfonic acid of 3, -diaminodibenzothiophenedioxide, which comprisesadmixing an aroyl halide and a mixture of the selected aminosulfonicacid and a steamvolatile tertiary amine in the presence of an inertorganic solvent under substantially anhydrous conditions; maintainingthe mixture under reaction conditions until reaction substantiallyceases and isolatingthe reaction product 3. A process according to claim2 in which the aminosulfonic acid is3,7-diaminodibenzothiophenedioxide-2,8-disulfonic acid.

4. A process according to claim 2 in which the amine is' atrialkylamine.

5. A process according to claim 2 in which the amine is pyridine.

6. The method of aroylating a sulfonic acid of"3,7-diaminodibenzothiophenedioxide, which comprises admixing an aroylhalide and a salt of said aminosulfonic acid and a steam-volatiletertiary amine-in the presence of an inert organic solvent undersubstantially anhydrous conditions; maintaining the mixture underreaction conditions until reaction substantially ceases; and isolatingthe reaction product.

' 7. A process according to claim 6 in which the aminosulfonic acid is3,7-diaminodibenzothiophenedioxide-2,8-disulfonic acid.

8. A process according to claim 6 in which the amine is a trialkylamine.

9. A process according to claim 6 in which the amine is pyridine.

MARIO SCALERA. WARREN S. FORSTER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,497,130 Lubs Feb. 14, 19502,497,131 Lubs Feb. 14, 1950

1. THE METHOD OF ACYLATING A SULFONIC ACID OF3,7-DIAMINODIBENZOTHIOPHENEDIOXIDE WHICH COMPRISES ADMIXING AND AROYLHALIDE AND A MEMBER FROM THE GROUP OF (A) MIXTURES OF THE SELECTEDAMINOSULFONIC ACID WITH A STEAM-VOLATILE TERTIARY AMINE, AND (B) SALTSOF A STEAM-VOLATILE TERTIARY AMINE AND THE SELECTED AMINOSULFONIC ACID,IN THE PRESENCE OF AN INERT ORGANIC SOLVENT UNDER SUBSTANTIALLYANHYDROUS CONDITIONS; MAINTAINING THE MIXTURE UNDER REACTION CONDITIONSUNTIL REACTION SUBSTANTIALLY CEASES AND ISOLATING THE REACTION PRODUCT.